Pre Exam # 2 Lecture Flashcards
Q # 2 It was stated that the patient, Robert had a wide range of auto-antibodies against various organ specific antigens as well as the liver and skin. How might a defect in normal T cell development lead to auto-antibody production?
No AIRE means no presentation of peptides by thymic medullary epithelial cells. single positive thymocytes cannot undergo negative selection, escape to the periphery, and are able to react with self peptides.
What type of signal induces positive selection?
Weak signal
What type of signal induces negative selection?
Strong Signal
What type of signal produces Treg?
Intermediate signal, causes up regulation of FoxP3; Treg moves to the periphery and suppresses self reactive T cells.
Experiments demonstrating negative selection showed that TCR transgenic mice specific for H-Y antigens were deleted in _________ mice
Male transgenic mice
Name the three cell surface proteins expressed at the double positive stage?
CD4, CD8, a,b, CD3, complete TCR.
Whats at the double negative stage?
CD44, CD25, Kit, pre TCR (rearranged beta chain, PreTalpha)
Chaperone proteins that help stabilize class I in the ER include…
Calnexin, Calreticulin, ERP57, ERAP
Tapasin
anchors MHC I w/TAP to each other.
Peptide binding clefts in class II molecules differ from those in class I molecules in these 2 important ways
Class II has a larger peptide binding cleft (12-16, but upwards of 30+); Class II has four peptide binding clefts in the center; Class II has alpha and beta chain/ Class I has 8 -10 aa binding cleft, shorter, binds two anchor residues towards outside, made up of alpha and b2m chain.
TCR resemble the ________ of antibody molecules
Fab
This protein is required at the pre T cell stage to induce signaling
CD3 is the signaling portion
Most of the variability found in the TCR is found in this region
in the peptide binding region; CDR3
Name the two areas of the thymus that are important for positive and negative selection
positive selection occurs in the cortex; negative selection occurs in the medulla
A mechanism by which exogenous proteins can be processed and presented to CD8 T cells is known as
Cross presentation (exception to rule # 1); done by DCs; exception to rule #2 autophagy.
This cell type is responsible for positive selection
Thymic cortical epithelial cells.
This type is responsible for negative selection
Bone derived DCs and macrophages
If AIRE is expressed, this cell type plays a role in negative selection
Thymic medullary epithelial cells
CD4 T cells express a surface protein that interacts with and binds to this
MHC II
What does CD8 bind to?
MHC I
At the pre T cell stage, the pre-TCR signals the cell to block ( 1 of four things pre-TCR does)
further b chain rearrangement; alleic exclusion
Pre-TCR also signals to initiate (3 things)
alpha chain rearrangement, induces the expression of CD4/CD8, induces proliferation
Class I molecules consists of an alpha chain and a
b2m chain (invariant)
HLA-DM functions to help class II anitgen processing by
peptide editing, removing CLIP
TCR contacts both the MHC molecule and
peptide
Most T cell receptors are comprised of _________ and blank______
alpha and beta proteins/ 5% gamma delta
Positive selection occurs at this stage of development and assures that the mature T cells are
cortex at the double positive stage; assures that the mature T cells are MHC restricted
What is the process that makes thymocytes T cell tolerant
negative selection
Deficiency in this ER residing protein leads to an absence of CD8 T cells
TAP1&2/MHC I deficiency; no CD8 T cells
The pre TCR is expressed at this stage
double negative ( DN3-4)
Class I molecules accommodate peptides of this length
8-10aa; class II 15-30
This transcription factor is important to commit HSCs to the T Cell lineage
Notch-1
Multiple alleles at each locus of the gene encoding the HLA in a population as a whole is known as
as polymorphism – for class II, most of the polymorphism occurs in the beta chain
Polygenic vs polymorphism
How many different HLA molecules do your cells expressed – three class I and three class II (the polygenic is that there are three different class I and class II molecules)
This transcription factor regulates expression of tissue specific antigens for tolerance induction
AIRE
